The ability to track the location or identity of a component or item of interest has presented a significant challenge for industry and science. For example, the demands of keeping track of consumer products, such as items in a grocery store or jewelry, and the interest in identification devices, such as security cards, has led to the need for a secure and convenient system. Additionally, emerging technologies such as combinatorial chemistry, genomics research, and microfluidics also require the ability to identify and track the location of large numbers of items.
A traditionally used method for tracking the location or identity of a component or item of interest is Universal Product Code technology, or barcode technology, which uses a linear array of elements that are either printed directly on an object or on labels that are affixed to the object. These bar code elements typically comprise bars and spaces, with bars of varying widths representing strings of binary ones and spaces of varying widths representing strings of binary zeros. Bar codes can be detectable optically using devices such as scanning laser beams or handheld wands, or they can be implemented in magnetic media. The readers and scanning systems electro-optically decode the symbol to multiple alpha-numerical characters that are intended to be descriptive of the article or some characteristic thereof. Such characters are typically represented in digital form as an input to a data processing system for applications in point-of-sale processing and inventory control to name a few.
Although traditional bar codes typically only contain five or six letters or digits, two dimensional barcodes have also been developed in which one-dimensional bar codes are stacked with horizontal guard bars between them to increase the information density. For example, U.S. Pat. No. 5,304,786 describes the use of a high density two-dimensional bar code symbol for use in bar code applications. Unfortunately, although the information density of barcode technology has improved, this technology is often easily destructible, and the interference of dust, dirt and physical damage limits the accuracy of the information acquired from the readout equipment. Additionally, because of the difficulty of etching the barcode on many items, it is also difficult to apply to a wide range of uses.
Another technology that has been developed for labeling objects includes a composition comprising silicon or silicon dioxide microparticles and a powder, fluid or gas to be applied to objects such as vehicles, credit cards and jewelry (WO 95/29437). This system typically allows the formation of 200 million particles on a single wafer, each of the particles on one wafer being designed to be of identical shape and size so that when the particles are freed from the wafer substrate one is left with a suspension containing a single particle type which can thus be identified and associated with a particular item of interest. This system, although information dense, is also not practical for a wide range of application. One of the advantages explicitly stated in the application includes the unlikely event of unauthorized replication of the particles because of the non-trivial process of micromachining used which requires specialized equipment and skills. Thus, this process would not be widely amenable to a range of uses for inventory control.
In addition to abovementioned barcoding and microparticle inventory control schemes, emerging technologies such as combinatorial chemistry have also resulted in the development of various encoding schemes (See, for example, Czamik, A. W., xe2x80x9cEncoding Methods for Combinatorial Chemistryxe2x80x9d, Curr. Opin. Chem. Biol., 1997, 1, 60). The need for this development has arisen in part from the split and pool technique utilized in combinatorial chemistry to generate libraries on the order of one million compounds. Split and pool synthesis involves dividing a collection in beads into N groups, where N represents the number of different reagents being used in a particular reaction stage, and after the reaction is performed, pooling all of these groups together and repeating the split and pool process until the desired reaction sequence is completed. Clearly, in order to keep track of each of the compounds produced from a reaction series, the beads must be xe2x80x9ctaggedxe2x80x9d or encoded with information at each stage to enable identification of the compound of interest or the reaction pathway producing the compound. The tags used to encode the information, however, must be robust to the conditions being employed in the chemical synthesis and must be easily identifiable to obtain the information. Exemplary encoding techniques that have been developed include the use of chemically robust small organic molecules (xe2x80x9ctagsxe2x80x9d) that are cleaved from the bead after the synthesis is completed and analyzed using mass spectroscopy. (U.S. Pat. Nos. 5,565,324; 5,721,099). The disadvantage of this method is that the xe2x80x9ctagsxe2x80x9d must be cleaved from the bead in order to gain information about the identity of the compound of interest.
In response to this, several groups have developed encoding schemes that allow analysis while the xe2x80x9ctagsxe2x80x9d are still attached to the supports. For example, Radiofrequency Encoded Combinatorial (REC(trademark)) chemistry combines recent advances in microelectronics, sensors, and chemistry and uses a Single or Multiple Addressable Radiofrequency Tag (SMART(trademark)) semiconductor unit to record encoding and other relevant information along the synthetic pathway (Nicolaou et al., Angew. Chem. Int. Ed. Engl. 1995, 34, 2289). The disadvantage of this system, however, is that the SMART(trademark) memory devices utilized are very large in size (mm), and thus scanning the bead to decode the information becomes difficult. Another example of on-bead decoding includes the use of colored and fluorescent beads ( Egner et al., Chem. Commun. 1997, 735), in which a confocal microscope laser system was used to obtain the fluorescence spectra of fluorescent dyes. The drawback of this method, however, is the tendency of the dyes to undergo internal quenching by either energy transfer or reabsorption of the emitted light. Additionally, this system is not able to uniquely and distinctly identify a range of dyes.
Clearly, it would be desirable to develop a general information dense encoding system flexible, robust and practical enough to be utilized both in general inventory control and in emerging technologies. This system would also be capable of distinctly and uniquely identifying particular items or components of interest.
The present invention provides a novel encoding system and methods for determining the location and/or identity of a particular item or component of interest. In particular, the present invention utilizes a xe2x80x9cbarcodexe2x80x9d comprising one or more particle size distributions of semiconductor nanocrystals (quantum dots) having characteristic spectral emissions to either xe2x80x9ctrackxe2x80x9d the location of a particular item of interest or to identify a particular item of interest. The semiconductor nanocrystals used in the inventive xe2x80x9cbarcodingxe2x80x9d scheme can be tuned to a desired wavelength to produce a characteristic spectral emission by changing the composition and size of the quantum dot. Additionally, the intensity of the emission at a particular characteristic wavelength can also be varied, thus enabling the use of binary or higher order encoding schemes. The information encoded by the quantum dot can be spectroscopically decoded, thus providing the location and/or identity of the particular item or component of interest.
In a particularly preferred embodiment, the method involves providing a composition comprising an item of interest, and one or more sizes of semiconductor nanocrystals having characteristic spectral emissions, or providing a composition comprising a support, an item of interest, and one or more sizes of semiconductor nanocrystals; subjecting said composition to a primary light source to obtain the spectral emissions for said one or more sizes of quantum dots on said composition; and correlating said spectral emission with said item of interest. The present method, in preferred embodiments, can be used to encode the identity of biomolecules, particularly DNA sequences, or other items, including, but not limited to, consumer products, identification tags and fluids.
In another aspect, the present invention provides compositions. In one particularly preferred embodiment, the composition comprises a support, and one or more particle size distributions of semiconductor nanocrystals having different characteristic spectral emissions. In another particularly preferred embodiment, the composition comprises a support, one or more items of interest and one or more sizes of quantum dots having different characteristic spectral emissions. In yet another preferred embodiment, the composition comprises an item of interest and one or more sizes of quantum dots having different characteristic spectral emissions. The quantum dots can be associated with, attached thereto, or embedded within said support structure. Additionally, the quantum dot can optionally have an overcoating comprised of a material having a band gap greater than that of the quantum dot.
In yet another aspect, the present invention provides libraries of compounds and/or items of interest. In a particularly preferred embodiment, each compound in the library is bound to an individual support, and each support has attached thereto or embedded therein one or more identifiers comprising one or more particle size distributions of quantum dots having characteristic spectral emissions. In yet another preferred embodiment, each item of interest has attached thereto, or embedded therein one or more identifiers comprising one or more particle size distributions of quantum dots having characteristic spectral emissions.
In yet another aspect, the present invention also provides kits for identifying an item of interest comprising a collection of items of interest, and wherein each member of said collection of objects has attached thereto or embedded therein one or more particle size distributions of quantum dots having characteristic spectral emissions. In another preferred embodiment, the kit comprises a collection of item is of interest, each bound to a solid support, wherein each support has attached thereto, associated therewith, or embedded therein one or more unique identifiers.
In another aspect, the present invention provides methods for identifying a compound having a particular characteristic of interest comprising providing a library of compounds, testing said library of compounds for a particular characteristic of interest, observing the photoluminescence spectrum for each identifier attached to each support containing a compound of interest, and identifying the compound of interest by determining the reaction sequence as encoded by said one or more sizes of quantum dots. In yet another particularly preferred embodiment, the step of identifying the reaction sequence can be determined before testing the library of compounds because the reaction sequence can be recorded during the synthesis of the compound by xe2x80x9creadingxe2x80x9d the beads (i.e., observing the photoluminescence spectrum) prior to each reaction step to record the reaction stages. The present invention additionally provides methods for recording the reaction stages of a synthesis concurrently with the synthesis.
In yet another aspect, the present invention provides methods for identifying a molecule having a characteristic of interest comprising contacting a first library of molecules with a second library of molecules, wherein each of the molecules in the first library is encoded using one or more sizes of quantum dots and the second library has attached thereto or embedded therein one or more sizes of quantum dots acting as xe2x80x9cprobesxe2x80x9d. This method provides simultaneously a way to identify the binding of one or more molecules from the second library to the first library and determining the structure of said one or more molecules from the first library.
xe2x80x9cQuantum dotxe2x80x9d: As used herein, the term xe2x80x9cquantum dotxe2x80x9d means a semiconductor nanocrystal with size dependent optical and electrical properties. In particular, the band gap energy of a quantum dot varies with the diameter of the crystal.
xe2x80x9cIdentification unit or barcodexe2x80x9d: As used herein, the term xe2x80x9cidentification unitxe2x80x9d is used synonymously with the term xe2x80x9cbarcodexe2x80x9d, and comprises one or more sizes of quantum dots, each size of quantum dot having a characteristic emission spectrum. The xe2x80x9cidentification unitxe2x80x9d or xe2x80x9cbarcodexe2x80x9d enables the determination of the location or identity of a particular item or matter of interest.
xe2x80x9cItem of interestxe2x80x9d: As used herein, the term xe2x80x9citem of interestxe2x80x9d is used synonymously with the term xe2x80x9ccomponent of interestxe2x80x9d and refers to any item, including, but not limited to, consumer item, fluid, gas, solid, chemical compound, and biomolecule.
xe2x80x9cBiomoleculexe2x80x9d: As used herein, the term xe2x80x9cbiomoleculexe2x80x9d refers to molecules (e.g., proteins, amino acids, nucleic acids, nucleotides, carbohydrates, sugars, lipids, etc.) that are found in nature.
xe2x80x9cOne or more sizes of quantum dotsxe2x80x9d: As used herein, the phrase xe2x80x9cone or more sizes of quantum dotsxe2x80x9d is used synonymously with the phrase xe2x80x9cone or more particle size distributions of quantum dotsxe2x80x9d. One of ordinary skill in the art will realize that particular sizes of quantum dots are actually obtained as particle size distributions.